PURPOSE: Topotecan is widely used for refractory solid tumors but multi-drug resistance may occur due to tumor expression of ATP-binding cassette (ABC) transporters. Since erlotinib, an inhibitor of the epidermal growth factor receptor, also inhibits several ABC transporters, we performed a phase I study to evaluate the safety, efficacy, and pharmacokinetics of intravenous topotecan given in combination with erlotinib. METHODS: Patients received 150 mg of oral erlotinib daily and a 30 min intravenous infusion of topotecan on days 1-5 of a 21-day cycle. Dosage escalation of topotecan occurred with a starting dosage of 0.75 mg/m(2). The pharmacokinetics of topotecan was evaluated on day 1 of cycle 1 without erlotinib and on day 1 of cycle 2 or 3 with erlotinib. RESULTS: Twenty-nine patients were enrolled. The maximum tolerated dosage was determined to be 1.0 mg/m(2). Dose-limiting toxicities included neutropenia and thrombocytopenia. The average duration of treatment was 97 days. Two partial responses were observed. Topotecan clearance and exposure were similar with and without erlotinib. CONCLUSIONS: The combination of topotecan and erlotinib is tolerable at clinically effective doses. Erlotinib does not affect the disposition of topotecan to a clinically significant extent.
PURPOSE:Topotecan is widely used for refractory solid tumors but multi-drug resistance may occur due to tumor expression of ATP-binding cassette (ABC) transporters. Since erlotinib, an inhibitor of the epidermal growth factor receptor, also inhibits several ABC transporters, we performed a phase I study to evaluate the safety, efficacy, and pharmacokinetics of intravenous topotecan given in combination with erlotinib. METHODS:Patients received 150 mg of oral erlotinib daily and a 30 min intravenous infusion of topotecan on days 1-5 of a 21-day cycle. Dosage escalation of topotecan occurred with a starting dosage of 0.75 mg/m(2). The pharmacokinetics of topotecan was evaluated on day 1 of cycle 1 without erlotinib and on day 1 of cycle 2 or 3 with erlotinib. RESULTS: Twenty-nine patients were enrolled. The maximum tolerated dosage was determined to be 1.0 mg/m(2). Dose-limiting toxicities included neutropenia and thrombocytopenia. The average duration of treatment was 97 days. Two partial responses were observed. Topotecan clearance and exposure were similar with and without erlotinib. CONCLUSIONS: The combination of topotecan and erlotinib is tolerable at clinically effective doses. Erlotinib does not affect the disposition of topotecan to a clinically significant extent.
Authors: Fred F Kadlubar; Gertrud S Berkowitz; Robert R Delongchamp; Charles Wang; Bridgett L Green; George Tang; Jatinder Lamba; Erin Schuetz; Mary S Wolff Journal: Cancer Epidemiol Biomarkers Prev Date: 2003-04 Impact factor: 4.254
Authors: Julio E Diestra; George L Scheffer; Isabel Català; Marc Maliepaard; Jan H M Schellens; Rik J Scheper; Jose R Germà-Lluch; Miguel A Izquierdo Journal: J Pathol Date: 2002-10 Impact factor: 7.996
Authors: Charis P Zamber; Jatinder K Lamba; Kazuto Yasuda; Jennifer Farnum; Kenneth Thummel; John D Schuetz; Erin G Schuetz Journal: Pharmacogenetics Date: 2003-01
Authors: Denis Soulieres; Neil N Senzer; Everett E Vokes; Manuel Hidalgo; Sanjiv S Agarwala; Lillian L Siu Journal: J Clin Oncol Date: 2004-01-01 Impact factor: 44.544
Authors: C M F Kruijtzer; J H Beijnen; H Rosing; W W ten Bokkel Huinink; M Schot; R C Jewell; E M Paul; J H M Schellens Journal: J Clin Oncol Date: 2002-07-01 Impact factor: 44.544